A new metal binding domain involved in cadmium, cobalt and zinc transport
The P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, but bioinformatics analyses indicate that a diversity of MBDs may exist in nature. In this paper, we report the biochemical, structural and functional characterization of a new MBD from the Cupriavidus metallidurans P1B-4-ATPase CzcP (CzcP MBD). The CzcP MBD binds two Cd2+, Co2+ or Zn2+ ions in distinct and unique sites and adopts an unexpected fold consisting of two fused ferredoxin-like domains. Both in vitro and in vivo activity assays using full-length CzcP, truncated CzcP and several variants indicate a regulatory role for the MBD and distinct functions for the two metal binding sites. Finally, taken together, these findings elucidate a previously unknown MBD and suggest new regulatory mechanisms for metal transport by P1B-ATPases.
- Northwestern Univ., Evanston, IL (United States). Dept. of Molecular Biosciences. Dept. of Chemistry
- Wayne State Univ., Detroit, MI (United States). School of Medicine. Dept. of Pharmaceutical Sciences. Cardiovascular Research Inst.
- Publication Date:
- OSTI Identifier:
- Grant/Contract Number:
- AC02-98CH10886; GM58518; DK068139; F32GM105339; T32HL120822
- Accepted Manuscript
- Journal Name:
- Nature Chemical Biology
- Additional Journal Information:
- Journal Volume: 11; Journal Issue: 9; Journal ID: ISSN 1552-4450
- Nature Publishing Group
- Research Org:
- Northwestern Univ., Evanston, IL (United States)
- Sponsoring Org:
- USDOE; National Inst. of Health (NIH) (United States)
- Contributing Orgs:
- Wayne State Univ., Detroit, MI (United States)
- Country of Publication:
- United States
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Bioinorganic chemistry; Metals; Transporters; X-ray crystallography
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